Validation of Case-Finding Algorithms Derived from Administrative Data for Identifying Adults Living with Human Immunodeficiency Virus Infection

OBJECTIVE: We sought to validate a case-finding algorithm for human immunodeficiency virus (HIV) infection using administrative health databases in Ontario, Canada. METHODS: We constructed 48 case-finding algorithms using combinations of physician billing claims, hospital and emergency room separations and prescription drug claims. We determined the test characteristics of each algorithm over various time frames for identifying HIV infection, using data abstracted from the charts of 2,040 randomly selected patients receiving care at two medical practices in Toronto, Ontario as the reference standard. RESULTS: With the exception of algorithms using only a single physician claim, the specificity of all algorithms exceeded 99%. An algorithm consisting of three physician claims over a three year period had a sensitivity and specificity of 96.2% (95% CI 95.2%-97.9%) and 99.6% (95% CI 99.1%-99.8%), respectively. Application of the algorithm to the province of Ontario identified 12,179 HIV-infected patients in care for the period spanning April 1, 2007 to March 31, 2009. CONCLUSIONS: Case-finding algorithms generated from administrative data can accurately identify adults living with HIV. A relatively simple "3 claims in 3 years" definition can be used for assembling a population-based cohort and facilitating future research examining trends in health service use and outcomes among HIV-infected adults in Ontario

Predictors of linkage to care following community-based HIV counseling and testing in rural Kenya

Despite innovations in HIV counseling and testing (HCT), important gaps remain in understanding linkage to care. We followed a cohort diagnosed with HIV through a community-based HCT campaign that trained persons living with HIV/AIDS (PLHA) as navigators. Individual, interpersonal, and institutional predictors of linkage were assessed using survival analysis of self-reported time to enrollment. Of 483 persons consenting to follow-up, 305 (63.2%) enrolled in HIV care within 3 months. Proportions linking to care were similar across sexes, barring a sub-sample of men aged 18–25 years who were highly unlikely to enroll. Men were more likely to enroll if they had disclosed to their spouse, and women if they had disclosed to family. Women who anticipated violence or relationship breakup were less likely to link to care. Enrolment rates were significantly higher among participants receiving a PLHA visit, suggesting that a navigator approach may improve linkage from community-based HCT campaigns.Vestergaard Frandse

Mortality by causes in HIV-infected adults: comparison with the general population

<p>Abstract</p> <p>Background</p> <p>We compared mortality by cause of death in HIV-infected adults in the era of combined antiretroviral therapy with mortality in the general population in the same age and sex groups.</p> <p>Methods</p> <p>Mortality by cause of death was analyzed for the period 1999-2006 in the cohort of persons aged 20-59 years diagnosed with HIV infection and residing in Navarre (Spain). This was compared with mortality from the same causes in the general population of the same age and sex using standardized mortality ratios (SMR).</p> <p>Results</p> <p>There were 210 deaths among 1145 persons diagnosed with HIV (29.5 per 1000 person-years). About 50% of these deaths were from AIDS. Persons diagnosed with HIV infection had exceeded all-cause mortality (SMR 14.0, 95% CI 12.2 to 16.1) and non-AIDS mortality (SMR 6.9, 5.7 to 8.5). The analysis showed excess mortality from hepatic disease (SMR 69.0, 48.1 to 78.6), drug overdose or addiction (SMR 46.0, 29.2 to 69.0), suicide (SMR 9.6, 3.8 to 19.7), cancer (SMR 3.2, 1.8 to 5.1) and cardiovascular disease (SMR 3.1, 1.3 to 6.1). Mortality in HIV-infected intravenous drug users did not change significantly between the periods 1999-2002 and 2003-2006, but it declined by 56% in non-injecting drug users (<it>P </it>= 0.007).</p> <p>Conclusions</p> <p>Persons with HIV infection continue to have considerable excess mortality despite the availability of effective antiretroviral treatments. However, excess mortality in the HIV patients has declined since these treatments were introduced, especially in persons without a history of intravenous drug use.</p

Molecular evolution of vertebrate sex-determining genes

Y-linked Dmy (also called dmrt1bY) in the teleost fish medaka, W-linked Dm-W in the African clawed frog (Xenopus laevis), and Z-linked Dmrt1 in the chicken are all sex chromosome-linked Dmrt1 homologues required for sex determination. Dmy and Dm-W both are Dmrt1 palalogues evolved through Dmrt1 duplication, while chicken Dmrt1 is a Z-linked orthologue. The eutherian sex-determining gene, Sry, evolved from an allelic gene, Sox3. Here we analyzed the exon–intron structures of the Dmrt1 homologues of several vertebrate species through information from databases and by determining the transcription initiation sites in medaka, chicken, Xenopus, and mouse. Interestingly, medaka Dmrt1 and Dmy and Xenopus Dm-W and Dmrt1 have a noncoding-type first exon, while mouse and chicken Dmrt1 do not. We next compared the 5′-flanking sequences of the Dmrt1 noncoding and coding exons 1 of several vertebrate species and found conservation of the presumptive binding sites for some transcription factors. Importantly, based on the phylogenetic trees for Dmrt1 and Sox3 homologues, it was implied that the sex-determining gene Dmy, Dm-W, and Sry have a higher substitution rate than thier prototype genes. Finally, we discuss the evolutionary relationships between vertebrate sex chromosomes and the sex-determining genes Dmy/Dm-W and Sry, which evolved by neofunctionalization of Dmrt1 and Sox3, respectively, for sex determining function. We propose a coevolution model of sex determining gene and sex chromosome, in which undifferentiated sex chromosomes easily allow replacement of a sex-determining gene with another new one, while specialized sex chromosomes are restricted a particular sex-determining gene

Patterns, trends and sex differences in HIV/AIDS reported mortality in Latin American countries: 1996-2007

<p>Abstract</p> <p>Background</p> <p>International cohort studies have shown that antiretroviral treatment (ART) has improved survival of HIV-infected individuals. National population based studies of HIV mortality exist in industrialized settings but few have been presented from developing countries. Our objective was to investigate on a population basis, the regional situation regarding HIV mortality and trends in Latin America (LA) in the context of adoption of public ART policies and gender differences.</p> <p>Methods</p> <p>Cause of death data from vital statistics registries from 1996 to 2007 with "good" or "average" quality of mortality data were examined. Standardized mortality rates and Poisson regression models by country were developed and differences among countries assessed to identify patterns of HIV mortality over time occurring in Latin America.</p> <p>Results</p> <p>Standardized HIV mortality following the adoption of public ART policies was highest in Panama and El Salvador and lowest in Chile. During the study period, three overall patterns were identified in HIV mortality trends- following the adoption of the free ART public policies; a remarkable decrement, a remarkable increment and a slight increment. HIV mortality was consistently higher in males compared to females. Mean age of death attributable to HIV increased in the majority of countries over the study period.</p> <p>Conclusions</p> <p>Vital statistics registries provide valuable information on HIV mortality in LA. While the introduction of national policies for free ART provision has coincided with declines in population-level HIV mortality and increasing age of death in some countries, in others HIV mortality has increased. Barriers to effective ART implementation and uptake in the context of free ART public provision policies should be further investigated.</p

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies